During the current budget year, we have demonstrated that tumor cells with a reduced content of DNA could be generated in vivo as a result of macrophage tumoricidal activity. Inoculation of pyran or Corynebacterium parvum i.p. in mice with Ehrlich ascites (EA) tumor cells induced a dramatic reduction in the EA tumor content of the peritoneal exudate. Cell cycle analysis of peritoneal exudate cell DNA content revealed that cells from untreated tumor-bearing mice possessed a DNA content approximately 4C to 8C, characteristic of aneuploid EA cells, while the pyran-\or C. parvum-treated animals had a larger complement of cells with a 2C DNA content and a loss of cells with an 8C DNA content. These results confirmed our previous demonstration of the induction in vitro of tumor cells of reduced ploidy as a result of macrophage tumoricidal activity and expanded that observation into an in vivo model. 5-Flurouracil (5-FUra) inoculated i.p. into Ehrlich ascites tumor-bearing (EATU) mice inhibited in vivo tumor cell proliferation and generated a population of EATU cells with half their normal content of DNA. The appearance of aberrant (approximately 2C) EATU cells from a normally aneuploid (approximately 4C) tumor cell line appeared to require a radiosensitive host cell population, since prior irradiation of animals later given injections of 5-FUra and EATU cells resulted in significantly fewer 2C tumor cells when compared with unirradiated tumor bearers. Further experiments are being conducted to confirm preliminary observations of macrophage-mediated host cell participation in the generation of tumor cells of reduced ploidy and in the alteration in the cell cycle distribution of the surviving tumor cells. Generation of tumor cells of reduced ploidy may be the cause or the result of a host-mediated tumoricidal mechanism. These results are consistent with a common macrophage-mediated mechanism of induction of tumor cells of reduced ploidy in mice inoculated with agents with directly activated macrophages and in mice inoculated with 5-FU. This is further substantiated by the demonstration of adherent cells with nonspecific tumoricidal activity in the peritoneal cavity of mice treated with Ehrlich ascites cells and 5-FU. In a second area, we have continued to charcterize the accessory cell function and antigen-presenting capacity of a series of Ia+ dendritic cell-like cell lines derived from the P388 leu-kemia. Our specific objectives for the coming year will be directed toward continued production and analysis of a series of monoclonal antibodies directed toward mouse macrophage antigens.